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Open Access 01-12-2012 | Research

Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation

Authors: Stephanos Kyrkanides, Sabine M Brouxhon, Ross H Tallents, Jen-nie H Miller, John A Olschowka, M Kerry O’Banion

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

This study evaluated whether GM₂ ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB^−/− mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB^−/− mice by the Thy1 promoter. Despite β-hexosaminidase restoration in neurons was sufficient in rescuing HexB^−/− mice from GM₂ neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM₂ presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored.

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Title: Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
Authors: Stephanos Kyrkanides
Sabine M Brouxhon
Ross H Tallents
Jen-nie H Miller
John A Olschowka
M Kerry O’Banion
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-186

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Springer Medicine

Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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